吸入用丹参总酚酸药物微粉的制备及其质量评价

Preparation and Quality Evaluation of Salvianolic Acids Micro Powder

目的:研究卵磷脂和精氨酸的加入对丹参总酚酸药物微粉粉体学性质的影响,筛选出粉体学性质较优的药物微粉。方法:拟沿用前期实验建立的丹酚酸B HPLC含量测定方法和微粉制备工艺,以丹参水溶性成分丹参总酚酸为模型药物,L-精氨酸为pH值调节剂,卵磷脂为添加剂,湿法球磨制备得到丹参总酚酸药物微粉。通过微观形态、粒径及其分布、流动性、吸湿性和体外沉积性对药物微粉进行质量评价。结果:筛选出Sal-Arg-2%药物微粉粉体学性质最优,其粒径小于5μm,D50为1.153μm,休止角为25.66°±1.24,在10 h和30 h后的吸湿增重为别为7.42%±0.05和11.02%±0.04,递送率为72.99%,微细粒子百分比为14.07%,MMAD为4.57μm。结论:精氨酸和卵磷脂的加入可改善丹参总酚酸药物微粉的粉体学性质,卵磷脂加入比例越大,粉体学性质越好,实验选择Sal-Arg-2%药物微粉为后续干粉吸入剂的制备提供物质基础。

Purpose：Study on lecithin and arginine on the effect of salvianolic acid drug powder properties, screen out the micro powder with better properties. Methods ：This study intends to use previous experiment to establish Salvianolic acids B determination method of HPLC and micropowder preparation process. Using Salvianolic acids as a model drug,the L-arginine to adjust Salvianolic acids pH and lecithin as the additive. Using the wet ball mill to prepare the Salvianolic acids micropowder. The microcosmic morphology, particle size and distribution, fluidity, hygroscopicity and extracorporeal deposition were used to evaluate the quality of Salvianolic acids micropowder. Results： Sal-Arg-2%micropowder powder was optimal. Its particle size less than 5 μm, D50 is 1.153 μm, repose angle is 25.66° ± 1.24, the hygroscopic weight are 7.42% ± 0.05 and 11.02% ± 0.04 after 10 h and 30 h, delivery rate is 72.99%, the fine particles percentage is 14.07%, MMAD is 4.57 μm. Conclusion： The addition of arginine and lecithin can improve the powdered properties of salvianolic acids, The greater amount of lecithin added, the better properties of the powder. Therefore, we selected Sal-Arg-2% micropowder as a material basis for the preparation of dry powder inhalation.